Asthma is a chronic respiratory disease affecting 8-13% of the U.S. population and characterized by airway hyperreactivity. Chronic infections are being identified with increasing frequency as causes of human morbidity and mortality. Pulmonary infection due to Mycoplasma pneumoniae has been associated with exacerbations of asthma and prolonged abnormalities in pulmonary functions following infection. Recent unpublished data has identified a subset of adult asthmatics who have experienced exacerbations of their asthma associated with M. pneumoniae infection which was both prolonged and failed to elicit a detectable antibody response. A number of cases of chronic mycoplasmal infection, both pulmonary and extrapulmonary, have been seen in adults and children with hypogammaglobulinemia indicating that humoral immunity is important in resolving infection with these organisms. Further, mycoplasmas are highly prevalent in patients in the late states of HIV infection, suggesting that the cellular arm of the immune response may likewise function in controlling such infections. We hypothesize that a subgroup of patients with asthma have inadequate or inappropriate immune responsiveness to mycoplasmas which results in chronic/recurrent infection. I propose to study the incidence of mycoplasmal infection in children with chronic asthma as well as the host immune response to the infection in order to determine whether differences exist from the population at large. I will examine the mechanisms by which the organism alters cell signaling and activation in vitro. Finally, I plan to investigate the effects of infection in a mouse model of asthma, which will permit the use of deletional mutant strains in the investigation of pathogenic mechanisms.